Abstract
Purpose:
Exudative age-related macular degeneration (AMD) represents the leading cause of lost vision in the elderly. Given that the pathology progresses at a slow pace, developing biomarkers is critical. In this regard, early disease detection prior to appearance of symptoms is crucial for rapid intervention and favorable prognosis. Recently, micro RNAs (miRNAs) have been recognized as potent biomarkers for a variety of human diseases including cancers, kidney diseases and acute myocardial infarction. While miRNAs are stable and present in a variety of body fluids including blood and urine, there is currently limited evidence for their presence in vitreous. We therefore decided to investigate in human patients the propensity of vitreal miRNAs to act as biomarkers for exudative AMD.
Methods:
In this pilot study, we obtained vitreous from patients suffering from neovascular AMD (n = 4) and non-vascular ocular pathology patients (n = 4). MicroRNA profiles in patient vitreous were obtained through micro-array analysis of 380 miRNAs using TaqMan® Array Human MicroRNA Cards (Applied Biosystems)
Results:
Of the 380 miRNAs analyzed, we obtained a significant difference in the expression of seven miRNAs in the vitreous of patients suffering from AMD. We noted an up regulation of miR146 and miR548a in all 4 AMD patients when compared to controls. Conversely, we saw a significant decrease in miRNAs miR16, miR106b, miR205, miR152 and miR24 in patients affected by exudative AMD. In line with a role in disease pathogenesis, miR16 negatively regulates VEGF levels. The observed decrease in miR16 is consistent with elevated VEGF levels in AMD. Confirmation of miRNA expression profiles is now in progress in additional patients.
Conclusions:
Our pilot data reveal that miRNAs may be promising biomarkers for the diagnosis of exudative AMD. Currently, patients suffering from AMD are diagnosed at late stages of disease when vision is already compromised. Our data suggests a specific miRNA signature could be obtained in the vitreous of patients suffering from AMD and used to determine onset of treatment. Micro-RNAs are stable RNA molecules that diffuse in circulation and are present in vitreous. The use of miRNAs to predict disease onset may be a potent tool.
Keywords: 412 age-related macular degeneration •
763 vitreous •
695 retinal degenerations: cell biology